title: Crystal structure analysis of the polysialic acid specific O-acetyltransferase NeuO.
abstract: The major virulence factor of the neuroinvasive pathogen Escherichia coli K1 is the K1 capsule composed of α2,8-linked polysialic acid (polySia). K1 strains harboring the CUS-3 prophage modify their capsular polysaccharide by phase-variable O-acetylation, a step that is associated with increased virulence. Here we present the crystal structure of the prophage-encoded polysialate O-acetyltransferase NeuO. The homotrimeric enzyme belongs to the left-handed β-helix (LβH) family of acyltransferases and is characterized by an unusual funnel-shaped outline. Comparison with other members of the LβH family allowed the identification of active site residues and proposal of a catalytic mechanism and highlighted structural characteristics of polySia specific O-acetyltransferases. As a unique feature of NeuO, the enzymatic activity linearly increases with the length of the N-terminal poly-ψ-domain which is composed of a variable number of tandem copies of an RLKTQDS heptad. Since the poly-ψ-domain was not resolved in the crystal structure it is assumed to be unfolded in the apo-enzyme.
authors.affiliation: Abteilung für Molekulare Strukturbiologie, Institut für Mikrobiologie und Genetik, Georg-August-Universität Göttingen, Göttingen, Germany.
authors.forename: Eike C
authors.initials: EC
authors.lastname: Schulz
authors.forename: Anne K
authors.initials: AK
authors.lastname: Bergfeld
authors.forename: Ralf
authors.initials: R
authors.lastname: Ficner
authors.forename: Martina
authors.initials: M
authors.lastname: Mühlenhoff
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D055162:Biocatalysis; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012794:Sialic Acids / Q000378:metabolism*; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D012794:Sialic Acids; C021319:polysialic acid; D000123:Acetyltransferases; C056307:NeuO protein, E coli